Iodine Antiseptics Safe for Patients With Documented Iodine Allergy Labels

Antiseptic Stewardship and the Challenge of Iodine Allergy Labels

Periprosthetic joint infection remains among the most catastrophic complications in orthopedic surgery, associated with a 5.5-fold increase in 10-year mortality and annual hospital costs projected to reach $1.85 billion by 2030 [1, 2]. Effective prevention relies heavily on standardized antiseptic protocols, such as nasal decolonization and intraoperative irrigation, which are designed to reduce the bioburden of common pathogens and disrupt microbial biofilms (complex communities of bacteria that adhere to prosthetic surfaces and resist systemic antibiotics) [3, 4]. While some meta-analyses suggest that chlorhexidine-alcohol is superior for general surgical site preparation, specific data in bone and joint surgery have indicated a potential advantage for iodophor-alcohol combinations [5]. Despite the clinical utility of these agents, surgeons frequently encounter patients with documented iodine allergy labels, often leading to the avoidance of povidone-iodine products due to concerns over anaphylaxis or severe cutaneous reactions [6]. A new prospective study now evaluates the safety of maintaining standard iodine-based protocols in patients with these documented sensitivities.

Standardized Povidone-Iodine Protocol in a Labeled Cohort

The researchers conducted a prospective observational study to evaluate the safety of using iodophors (antiseptic agents that use a carrier molecule to release iodine slowly over time) in patients with an Iodine Allergy Label undergoing primary total joint arthroplasty. This study, which enrolled participants from July 2024 to October 2025, addressed a critical clinical conflict in orthopedic surgery: the tension between infection prevention and allergy management. While povidone-iodine and iodophor-impregnated drapes are considered essential antiseptic measures for total joint arthroplasty, they are frequently withheld from patients with documented allergy labels. This avoidance occurs despite the fact that iodine is a well-accepted measure to reduce the incidence of both periprosthetic joint infections and general surgical site infections. To assess the risk of adverse reactions in this population, the study utilized a standardized operative workflow for all enrolled patients without deviation from the established protocol. This standard-of-care regimen included povidone-iodine nasal decolonization, the application of an iodophor-impregnated adhesive drape, and intraoperative lavage with diluted povidone-iodine. Before surgery, patients completed a detailed questionnaire to document the source, duration, and specific type of their reported allergic reactions. The researchers established the primary endpoint as the occurrence of any perioperative allergic reaction throughout the hospital stay, providing a rigorous measure of whether these iodine-containing products could be safely tolerated in a labeled population.

Deconstructing the Iodine Allergy Label

In many surgical settings, institutional policies or clinician caution prevent surgeons from using iodine-containing products when a patient has a documented allergy label. This practice persists even when the risk of cross-reactivity (a phenomenon where the immune system identifies different substances as similar, triggering an allergic response to both) is unproven or the label is based on a distant, self-reported history. To evaluate the clinical reality of these labels, the researchers analyzed a cohort of 1,211 primary total joint arthroplasty procedures, identifying 37 patients (3.1%) with a documented iodine allergy label. The nature of these reported sensitivities varied significantly. Only five patients (13.5%) had allergies confirmed by skin testing, while the majority of the cohort, 25 patients (67.6%), reported an allergy to contrast media. Additionally, four patients (10.8%) reported a specific allergy to betadine, and five patients (13.5%) carried a concurrent shellfish allergy label. Notably, these labels were often decades old, with a mean reported allergy duration of 27.9 years. The preoperative questionnaires revealed a high burden of self-reported symptoms that often do not align with true IgE-mediated hypersensitivity (a rapid, immune-driven allergic reaction that can lead to anaphylaxis) to povidone-iodine. Among the labeled cohort, 70% of patients reported more than one reaction type. The most frequent complaints included swelling (89.2%), mild itching (83.8%), nausea and vomiting (78.4%), and wheezing (78.4%). Other reported symptoms included severe itching (62.2%), difficulty breathing (59.5%), and rash (29.9%). Despite this high prevalence of reported severe symptoms, including respiratory distress and significant swelling, the study found that these historical labels did not predict perioperative complications.

Clinical Safety and Implications for Infection Prevention

The primary safety analysis revealed that the enrolled patients in this study had no allergic reactions to the iodophors used in the perioperative period. Despite the high prevalence of severe historical symptoms reported by the 37 patients with iodine allergy labels, including swelling in 89.2% and wheezing in 78.4% of the cohort, the standardized surgical workflow was completed without complication. Throughout the entire perioperative stay, which involved exposure to povidone-iodine nasal decolonization, iodophor-impregnated adhesive drapes, and intraoperative lavage with diluted povidone-iodine, no allergic reactions were observed in this study. These results indicate that historical allergy labels, which often stem from non-allergic reactions to contrast media or distant self-reported events, do not reliably predict adverse responses to topical or diluted povidone-iodine during surgery. The researchers concluded that iodophors are safe in iodine-allergic patients undergoing total joint arthroplasty. This finding has immediate implications for surgical site infection prophylaxis, as it suggests that clinicians can safely utilize povidone-iodine protocols even in patients with documented sensitivities. Ultimately, these findings challenge routine iodophor avoidance, supporting standardized antiseptic protocols to minimize periprosthetic joint infection. By adhering to these evidence-based measures rather than defaulting to alternative antiseptics that may be less effective, surgeons can maintain a high standard of care for infection prevention without increasing the risk of hypersensitivity reactions in labeled patients.

References

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2. Otero JE, Brown TS, Courtney PM, Kamath AF, Nandi S, Fehring KA. What’s New in Musculoskeletal Infection. Journal of Bone and Joint Surgery. 2022. doi:10.2106/jbjs.22.00183

3. Fernández-Rodríguez D, Cho J, Chisari E, Citardi MJ, Parvizi J. Nasal microbiome and the effect of nasal decolonization with a novel povidone-iodine antiseptic solution: a prospective and randomized clinical trial. Scientific Reports. 2024. doi:10.1038/s41598-023-46792-8

4. Caldwell MC, Hughes M, Wei F, et al. Promising applications of D-amino acids in periprosthetic joint infection. Bone Research. 2023. doi:10.1038/s41413-023-00254-z

5. Peel T, Watson E, Lee SJ. Randomised Controlled Trials of Alcohol-Based Surgical Site Skin Preparation for the Prevention of Surgical Site Infections: Systematic Review and Meta-Analysis. Journal of Clinical Medicine. 2021. doi:10.3390/jcm10040663

6. Li H, Wang D, Zhang W, et al. Potential side effects of antibacterial coatings in orthopaedic implants: A systematic review of clinical studies. Frontiers in Bioengineering and Biotechnology. 2023. doi:10.3389/fbioe.2023.1111386